Gbe  lanlversttB  of  Chicago 

FOUNDED  BY  JOHN  D.  ROCKEFELLER 


EFFECTS  OF  CERTAIN  SALTS  ON  KIDNEY 
EXCRETION,  WITH  SPECIAL  REFEft* 
ENCE  TO  GLYCOSURIA 


A DISSERTATION 

SUBMITTED  TO  THE  FACULTY  OF  THE  OGDEN  GRADUATE  SCHOOL 
~OF  SCIENCE,  IN  CANDIDACY  FOR  THE  DEGREE  OF 
DOCTOR  OF  PHILOSOPHY 

(department  of  physiology) 


BY 

ORVILLE  HARRY  BROWN 


CHICAGO 

THE  UNIVERSITY  OF  CHICAGO  PRESS 

1905 


XL  be  'CfrUversitE  of  Chicago 

FOUNDED  BY  JOHN  D.  ROCKEFELLER 


EFFECTS  OF  CERTAIN  SALTS  ON  KIDNEY 
EXCRETION,  WITH  SPECIAL  REFER- 
ENCE TO  GLYCOSURIA 


A DISSERTATION 

SUBMITTED  TO  THE  FACULTY  OF  THE  OGDEN  GRADUATE  SCHOOL 
OF  SCIENCE,  IN  CANDIDACY  FOR  THE  DEGREE  OF 
DOCTOR  OF  PHILOSOPHY 

(DEPARTMENT  OF  physiology) 


BY 

ORVILLE  HARRY  BROWN 


CHICAGO 

THE  UNIVERSITY  OF  CHICAGO  PRESS 

1905 


( 


Reprinted  from  the  American  Journal  of  Physiology. 

Vol.  X.  — March  i,  1904.  — No.  VII. 


EFFECTS  OF  CERTAIN  SALTS  ON  KIDNEY  EXCRETION, 
WITH  SPECIAL  REFERENCE  TO  GLYCOSURIA.1 

By  ORVILLE  HARRY  BROWN. 


\From  the  Hull  Physiological  Laboratory  of  the  University  of  Chicago .] 

TRANSIENT  glycosuria  occurs  under  a great  number  of  condi- 


‘IX-  tions  and  is  an  accompanying  symptom  of  more  or  less  import- 
ance in  a great  variety  of  maladies.  Experimentally  it  is  well  known 
that  a transient  increase  of  sugar  in  the  urine  can  be  produced  in  a 
variety  of  ways,  chief  of  which  are  the  use  of  phlorhizdin,  adrenalin 
chloride,  excessive  amounts  of  narcotics,  extirpation  of  the  pancreas, 
a puncture  of  the  fourth  ventricle,  and  by  large  amounts  of  sugar  taken 
into  the  alimentary  canal.  In  marked  diuresis  sugar  is  usually  found 
in  the  urine.  Jacobj  2 showed  that  in  rabbits  glycosuria  always 
accompanied  the  diuresis,  produced  by  caffein,  caffein  sulphate,  and 
theobromine.  Bock  and  Hoffman  3 found  sugar  in  the  urine  after 
intravenous  injections  of  large  quantities  of  a 1 per  cent  solution  of 
sodium  chloride.  Kessler  4 observed  that  sugar  was  constantly  in  the 
urine  of  cats  after  injections  of  sodium  carbonate. 

’ At  the  suggestion  of  Dr.  A.  P.  Mathews,  I undertook  a series  of 
experiments  to  ascertain  the  effect  of  salt  solutions  on  the  production 
of  diuresis,  and  on  the  excretion  of  sugar  by  the  kidneys.  If  the 
kidney  activities  are  influenced  by  ions  as  are  the  functions  of  other 

1 Since  this  paper  has  been  sent  to  the  Journal,  reprints  from  Dr.  Martin  H. 
Fischer,  of  a preliminary  report  in  the  University  of  California  Publications,  on 
“ The  Production  and  Suppression  of  Glycosuria  in  Rabbits  through  Electrolytes,” 
have  been  received.  It  is  certainly  gratifying  that  his  results,  as  far  as  reported, 
corroborate  mine.  I wish  to  say  that  practically  all  of  my  results  were  obtained 

^during  the  winter  quarter  of  1903,  and  have  been  publicly  announced  several  times 
by  Dr.  A.  P.  Mathews.  See  Yale  Medical  Journal,  June,  1903. 

2 Jacobj  : Archiv  fur  experimentelle  Pathologie  und  Pharmakologie,  1895, 
xxxv,  p.  213. 

3 Bock  and  Hoffman:  Archiv  fur  Anatomie  und  Physiologie,  1871,  i,  s.  550  > 
Jacobj  : Loc.  cit. 

4 Kessler  : Versuch  uber  die  Wirkung  einiger  Diuretics,  Dissertation,  1877, 
Dorpat;  Jacobj:  Loc.  cit. 


378 


# 


Effects  of  Certain  Salts  on  Kidney  Excretion.  379 

tissues  of  the  body,  then  we  have  reason  to  assume  that  the  renal 
excretion,  either  in  quality  or  quantity,  or  both,  would  be  increased 
by  some  ions  and  decreased  by  others.  Dr.  A.  P.  Mathews  1 has 
shown  that  nerve  fibres  are  stimulated  by  anions  and  depressed  by 
cations.  Loeb  2 has  shown  that  the  nature  of  the  ions  in  a solution 
in  which  a muscle  is  immersed  has  an  important  influence  on  the 
muscle  contraction.  Cole,3  and  Neilson  and  Brown 4 have  demon- 
strated that  the  activities  of  enzymes  and  catalytic  agents  are  retarded 
by  cations  and  accelerated  by  anions. 

Methods. 

Rabbits  were  employed  for  the  experiments.  A 6 per  cent  solution 
of  urethane  given  by  the  stomach  was  used  as  the  anesthetic,  1 J gm. 
being  given  per  kilo  weight.  The  solutions  used  were  injected  into 
the  jugular  vein.  The  urine  was  collected  from  a cannula  which  was 
inserted  into  the  bladder.  The  urine  was  tested  for  sugar,  qualita- 
tively by  Haines’s  5 solution,  fermentation,  and  the  polarimeter,  and 
quantitatively  by  either  Fehling’s  solution  or  the  polarimeter,  or  both. 
As  there  was  always  a possibility  of  sugar’s  being  produced  in  the 
urine,  by  the  operation  combined  with  the  anesthetic,  the  solutions 
were  not  injected  until  it  had  been  shown  that  there  was  no  glyco- 
suria, or  in  case  there  was  some,  until  the  urine  no  longer  gave  a test 
for  sugar.  There  were  but  a few  experiments  where  sugar  appeared 
after  the  operation  before  the  injection  of  a solution.  If  it  appeared, 
it  usually  disappeared  within  one  or  two  hours. 

The  experiments  given  below  were  repeated  a number  of  times 
with  similar  results.  In  some  of  the  phlorhizdin  experiments  calcium 
chloride  was  used  in  place  of  the  strontium  chloride.  It  had  practi- 
cally the  same  effect,  but  possibly  had  a greater  tendency  to  decrease 
the  amount  of  water  excreted.  There  is,  however,  a depression  of 
water  excretion  by  both  the  calcium  and  strontium  chlorides  when 
they  are  used  in  sufficient  quantities.  In  a number  of  cases  complete 
or  nearly  complete  anuria  was  produced  by  suddenly  increasing  the 

1 Mathews:  Science,  n.  s.,  1903,  No.  436,  p.  729. 

2 Loeb:  This  journal,  1900,  iii,  p.  383. 

3 Cole:  Journal  of  physiology,  1903,  xxx,  p.  281. 

4 Neilson  and  Brown  : This  journal,  1904,  x,  p.  225. 

5 Haines’s  solution  is  the  same  as  Fehling’s  solution  except  that  the  copper 
sulphate  and  alkali  are  kept  together,  with  sufficient  glycerine  added  to  dissolve 
the  copper  hydrate. 


1 


380 


Orville  Harry  Brown. 

amount  of  calcium  or  strontium  chloride  injected.  This  tendency  to- 
ward suppression  of  the  kidney  excretion  was  much  more  marked 
with  one  lot  of  rabbits  which  was  used  than  with  the  rest.  The  ex- 
planation for  this  I do  not  know.  Dr.  S.  A.  Matthews  1 has  observed 
that  anuria  can  be  produced  by  the  use  of  an  ™ solution  of  gold  chlo- 
ride. In  smaller  amounts  he  has  found  that  the  gold  chloride  inhibits 
the  excretion  of  sugar  produced  by  those  salts  which  produce  diuresis. 
It  was  also  observed  during  the  course  of  my  experiments  that  sodium 
acetate,  sodium  citrate,  and  barium  chloride  caused  a very  active  per- 
istalsis which  in  some  cases  resulted  in  the  defecation  of  a large 
amount  of  watery  faeces.  It  should  be  observed  that  sodium  chloride 
and  sodium  citrate  produce  a reducing  substance  in  the  urine,  even 
though  the  amount  of  urine  excreted  was  in  some  cases  very  much 
less  than  the  amount  of  the  solution  injected.  This  substance  in  the 
first  few  experiments  was  tested  only  by  the  use  of  Haines’s  solution. 
The  reduction,  however,  resembled  closely  that  resulting  from  a 
known  sugar,  placed  in  sugar-free  urine. 

Experiment  1.  — Rabbit,  weight,  2500  gms.  10  c.c.  urine  in  45  minutes.  No 
sugar.  20  c.c.  sodium  acetate  injected  slowly.  40  c.c.  of  urine 
excreted.  This  gave  a heavy  reduction  with  Haines’s  solution. 

Experiment  2. — Rabbit,  weight,  2100  gms.  8.45  to  9.30  a.m.,  14  c.c.  of  urine 
were  collected.  No  sugar.  At  9.30  a slow  injection  of  sodium  citrate 
was  begun.  Amount  excreted  was  practically  equal  to  amount  injected. 
This  urine  gave  a heavy  reduction  with  Haines’s  solution. 

Experiment  3.  — Rabbit,  weight,  1880  gms.  From  2.00  to  3.00  p.m.,  21  c.c.  of 
urine  were  excreted.  No  sugar.  From  3.00  to  3.20,  16  c.c.  of  an  ™ 
sodium  sulphate  were  injected.  At  4.30,  ij  hours  after  the  beginning  of 
the  injection,  43  c.c.  of  the  solution  had  been  injected,  and  185  c.c.  of 
urine  had  been  excreted.  This  urine  gave  a heavy  reduction  with  Haines’s 
solution. 

Experiment  — Rabbit,  weight,  1700  gms.  From  9.00  to  10.00  a.m.,  10  c.c. 
of  urine  were  collected.  No  glycosuria.  From  10.00  to  12.00,  20  c.c. 
of  § sodium  chloride  were  injected.  40  c.c.  of  urine  collected.  Heavy 
reduction  of  Haines’s  solution  was  produced  by  this  urine. 

Experiment  5.  — Rabbit,  weight,  1900  gms.  The  urine  following  the  operation 
gave  a marked  reduction  of  Haines’s  solution.  After  ij  hours  this 
had  disappeared.  During  the  next  hour  a mixture  of  50  c.c.  ^ sodium 


1 Personally  communicated. 


Effects  of  Certain  Salts  on  Kidney  Excretion . 381 

chloride,  25  c.c.  ? sodium  sulphate,  and  25  c.c.  ;f  sodium  citrate,  was 
injected.  87  c.c.  of  urine  were  collected,  and  sugar  was  shown  by 
Haines’s  solution  and  fermentation  to  be  present  in  considerable  quantities. 

Experiment  6.  — Rabbit,  weight,  1700  gms.  Reducing  substance  in  urine,  after 
the  operation.  From  10.00  to  12.00  injected  100  c.c.  of  an  ? solution 
of  sodium  chloride.  This  urine  produced  considerable  gas  on  fermenta- 
tion, and  gave  a heavy  reduction  with  Haines’s  solution.  From  12.00  to 
1.30,  97i  c.c.  of  ~i  sodium  chloride  and  2\  c.c.  of  ? calcium  chloride 
were  injected.  27J  c.c.  of  urine  were  collected,  and  on  fermentation  only 
a small  amount  of  gas  was  given  off,  and  on  treating  with  Haines’s  solution 
only  a slight  precipitate  was  produced.  From  1.30  to  3.00,  95  c.c.  of 
sodium  chloride  and  5 c.c.  of  ? calcium  chloride  were  injected.  50  c.c. 
of  urine  were  excreted.  Neither  fermentation  nor  reduction  of  Haines’s 
solution  took  place. 

Experiment  7. — Rabbit,  weight,  1500  gms.  8 c.c.  of  urine  from  10.00  to  1 1.00. 
No  sugar.  This  experiment  was  the  same  as  6,  except  strontium  chloride 
was  substituted  for  calcium  chloride.  The  sugar  which  was  produced  by 
the  sodium  chloride  was  prevented  by  the  addition  of  small  amounts  of 
strontium  chloride  to  the  sodium  chloride.  The  specific  gravity  of  urine 
was  1. 016  during  the  sodium  chloride  injection,  and  1.005  a^er  the  addi- 
tion of  the  strontium  chloride.  From  3.00  to  5.00,  injected  200  c.c.  of  a 
mixture 1 of  sodium  chloride,  sulphate,  and  citrate,  in  the  proportion  of 
50  c.c.  of  an  ? solution  of  the  first,  25  c.c.  of  an  ? solution  of  the  second, 
and  25  c.c.  of  an  solution  of  the  third.  275  c.c.  of  urine  were  removed. 
0.005  gm*  °f  sugar  per  c.c.  of  urine  were  shown  by  Fehling’s  solution  to 
be  present.  From  5.00  to  7.00  p.m.,  injected  200  c.c.  of  a solution  the 
same  as  the  one  mentioned  just  preceding,  except  that  in  100  c.c.  of  the 
mixture,  there  were  45  c.c.  of  sodium  chloride  instead  of  50  c.c.,  22 \ c.c. 
of  sodium  citrate  instead  of  25,  and  7J  c.c.  of  ? strontium  chloride  was 
added.  130  c.c.  of  urine  were  excreted.  By  the  same  test  as  above, 
0.002  gm.  of  sugar  per  c.c.  of  urine  were  shown  to  be  present.  The  last 
few  c.c.  of  urine  collected  gave  no  sugar  test. 

Experiment  8.  — Rabbit,  weight,  1710  gms.  No  sugar  in  urine  following  the 
operation.  Injected  slowly  a mixture  of  50  c.c.  of  f*  sodium  chloride, 
25  c.c.  of?  sodium  sulphate,  20  c.c.  of  sodium  citrate,  and  5 c.c.  of 
? calcium  chloride.  Test  for  sugar  in  urine  excreted  was  negative. 

1 This,  with  a small  amount  of  calcium  chloride,  is  the  combination  used  by 
Dr.  S.  A.  Matthews  for  producing  diuresis  and  successfully  applied  by  him  in  the 
treatment  of  tetanus. 


382  Orville  Harry  Brown . 

Experiment  9.  — Rabbit,  weight,  1330  gms.  Given  a subcutaneous  injection  of 
5 c.c.  of  a 2 per  cent  alcoholic  solution  of  phlorhizdin.  Sugar  was  found 
in  the  urine  after  20  hours. 

Experime7it  10.  — Rabbit,  weight,  1 540  gms.  No  sugar  an  hour  after  operation. 
From  11.30  to  1.30,  80  c.c.  of  sodium  chloride  and  20  c.c.  of  f stron- 
tium chloride  were  injected.  At  12.00,  5 c.c.  of  phlorhizdin,  the  same 
solution  as  used  above,  was  given  subcutaneously.  At  2.00,  50  c.c.  of 
urine  were  excreted.  No  glycosuria.  The  flow  of  urine  became  very 
slow,  and  50  c.c.  of  an  ™ sodium  chloride  were  injected,  and  by  6.00 
o’clock,  30  c.c.  of  urine  had  been  excreted.  Just  a very  slight  reduction 
occurred  when  treated  with  Haines’s  solution. 

Experiment  11.  — Rabbit,  weight,  1300  gms.  No  sugar  in  urine  for  an  hour 
after  operation.  From  10.30  a.m.  to  12.30  p.m.,  a mixture  of  a 95  c.c. 
of  sodium  chloride,  and  5 c.c.  strontium  chloride,  and  5 c.c.  of  the  phlo- 
rhizdin as  used  before,  was  injected.  Samples  of  urine  collected  up  to 
12.30  a.  m.  gave  only  in  two  or  three  cases  slight  traces  of  sugar. 

Experime?it  1 2.  — Rabbit,  weight,  1570  gms.  At  9. 1 5 there  was  a slight  amount 
of  reducing  substance.  None  at  10.45.  At  10.45,  injected  25  c.c.  of  an 
^ solution  of  sodium  chloride.  At  12.30,  27  c.c.  of  urine  were  excreted: 
No  sugar.  At  12.30,  injected  25  c.c.  sodium  chloride  and  J c.c.  phlorhizdin. 
Within  about  15  minutes  sugar  was  found  in  the  urine.  By  2.45,  30  c.c. 
of  urine  were  excreted,  the  last  samples  of  which  contained  no  sugar. 
The  urine,  tested  quantitatively  by  the  polariscope,  showed  that  0.2  gm.  of 
sugar  were  excreted.  My  readings  of  the  polariscope  were  verified  in 
every  case  by  Dr.  Guthrie.  At  3.00  injected  24  c.c.  of  ™ sodium  chlo- 
ride and  \ c.c.  of  phlorhizdin,  same  as  before  used.  By  5.20,  26  c.c.  of 
urine  had  been  excreted,  the  last  of  which  contained  no  sugar.  The 
amount  of  sugar  excreted  this  time,  tested  in  the  same  manner  as  before, 
was  0.05  gm. 


Summary  and  Conclusions. 

1.  An  solution  of  sodium  chloride,  an  ^ solution  of  sodium 
citrate,  an  solution  of  sodium  acetate,  and  an  solution  of  sodium 
sulphate,  as  observed  by  Dr.  S.  A.  Matthews 1 and  others,  and  corrobo- 
rated by  my  experiments,  produces  diuresis. 

2.  These  same  salts,  as  has  been  observed  by  Mock  and  Hoffman  2 
in  case  of  sodium  chloride,  produce  a glycosuria. 

1 Dr.  S.  A.  Matthews  : Personally  communicated. 

2 Mock  and  Hoffman  : Loc.  cit. 


Effects  of  Certain  Salts  on  Kidney  Excretion . 383 

3.  It  might  seem  that  the  diuresis  was  the  cause  of  the  glycosuria, 
except  that  by  an  addition  of  small  amounts  of  calcium  or  strontium 
chloride,  the  glycosuria  is  prevented  while  the  diuresis  still  exists. 

4.  Calcium  and  strontium  chlorides  likewise  decrease  or  totally 
inhibit  the  excretion  of  sugar  which  is  caused  by  the  injection  of 
phlorhizdin. 

5.  Since  diuresis  and  glycosuria  are  caused  by  those  salts  which 
have  been  found  by  Dr.  A.  P.  Mathews 1 to  stimulate  nerve,  and 
that  depression  of  these  activities  is  caused  by  salts  which  he  has 
found  to  depress  the  irritability  of  nerve,  we  may  assume  that  the 
anions  stimulate  the  renal  activities,  and  the  cations  depress  them. 

6.  It  was  not  ascertained  whether  the  glycosuria  caused  by  the 
salts  was  the  same  as  that  produced  by  phlorhizdin,  or  whether  the 
sugar  of  the  blood  was  increased.  Further  experiments  are  being 
carried  on  in  this  laboratory  to  determine  this,  and  to  ascertain  the 
practical  value  of  results  obtained. 

I take  this  opportunity  to  express  my  thanks  to  the  members  of  the 
laboratory,  especially  Dr.  A.  P.  Mathews  and  Dr.  S.  A.  Matthews. 


1 Dr.  A.  P.  Mathews:  Loc.cit. 


